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Clinical and molecular factors predict survival after surgery for recurrent glioblastoma multiforme

Ángel Rodríguez de Lope1 , Manuel Amosa1, Jesús Andrade2, Isabel Herrera3, Castalia Fernández4, M.Angeles Cañizares1, Manuela Mollejo5, José María Borrás6, Bárbara Meléndez7 Departments of Neurosurgery1, Medical Oncology2 , Radiology3, Pathology4, and Molecular Pathology Research Unit6 from Hospital Virgen de la Salud. Toledo Department of Oncology and Radiotherapy4. IMO. Toledo Department of Neurosurgery7 from Hospital General Universitario de Ciudad Real


INTRODUCTION
Impact of radical tumor resection as first line therapy in glioblastoma is beyond controversy. The significance of second resection in case of tumor-recurrence remains unclear. In 2010, Park and colleagues introduced a clinical scale to predict survival after repeat resection in an attempt to facilitate patient guidance. They reported that patient condition, tumor location and tumor size were predictors of outcome after repeated resection. They did not analize molecular caracteristics of tumors for address the impact in overall survival.

AIM
To identify specific clinical and molecular parameters that might be recommend second surgery as part of multimodality treatment in glioblastoma recurrences.

PATIENTS AND METHODS
We performed a retrospective analysis of our institutional database consisting of prospectively collected data from primary glioblastoma patients reoperated at our center. All patients selected were treated at first line with radical resection followed by chemo-radiotherapy as Stupp protocol. Tumor recurrence was defined as the appearance or enlargement since prior imaging of a contrast-enhancing mass on T1-weighted magnetic resonance imaging. All patients underwent maximal safe surgical resection of their recurrent tumors.
Clinical variables included age, KPS, presence of headaches or seizures, and time from initial diagnosis to recurrence. Radiographic variables included side and lobe of tumor location. Tumor volumes were calculated. Molecular parameters GCIMP-status, IDH-1, MGMT methilation, EGFR amplification, ATRX and p53 expression were determined. Patients were treated with second line chemotherapy after reoperation. The sole outcome measure was survival time from the date of operation for tumor recurrence to the date of death.
Kaplan-Meier survival analysis with logrank testing was used to determine the prognostic significance of the parameters. Analyses were performed using PASW Statistics 20.0 (SPSS Inc, Chicago,IL).

RESULTS
We identified 55 patients (35 and 20, men and women respectively) treated between 2004 and 2012. Overall survival was 20,6 months ( range 7,7-76) Median age was of 52 years (range 24-78). Frontal (22%), parietal (30%) and temporal (35%) lobe affectations were represented in this sample set. Younger age, KPS > 80 and tumor volume < 40 cc. at recurrence were favorable clinical factors. Overall survival in positive ATRX patients was 26 months. G-CIMP status, IDH-1 mutation and MGMT methylation was associated with long term survival in reoperated patients.

CONCLUSIONS
Our findings suggest benefits of second surgery in patients with prognostically favorable clinical factors, such as the younger age at diagnosis and molecular factors as IDH-1, GCIMP positive status and MGMT methylation. In these patients reintervention might improve benefits of second line chemotherapy treatments

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